tbuckley/cabot-search huggingface dataset:
Association of Problematic Anger With Long-term Adjustment Following the Military-to-Civilian Transition
Authors: Amy B. Adler, Cynthia A. LeardMann, Javier Villalobos, Isabel G. Jacobson, David Forbes, Jenn Belding, Satbir Boparai, Felicia Carey, Sheila Castañeda, Toni Rose Geronimo-Hara, Claire Kolaja, Sandra Magallon, Anna Rivera, Rudolph Rull, Julia Seay, Neika Sharifian, Beverly Sheppard, Daniel Trone, Jennifer Walstrom, Nikki Wooten, Katie Zhu
Journal: JAMA Network Open (2022)

Few studies have examined the role of problematic anger in long-term adjustment of service members transitioning out of the military.To determine the prevalence of problematic anger during the military-to-civilian transition period and the association of problematic anger with adjustment to civilian life.This cohort study used 2 waves of survey data administered approximately 5 years apart (time 1 [T1; September 26, 2014, to August 25, 2016] and time 2 [T2; October 23, 2019, to August 31, 2021]) from the Millennium Cohort Study, a population-based military study. Participants were US active-duty service members within 24 months of separating from military service at T1. Statistical analysis was performed from September 2021 to May 2022.Problematic anger was operationalized as scoring at least 12 points on the 5-item Dimensions of Anger Reactions scale at T1.Behavioral and functional health (depression, posttraumatic stress disorder, problem drinking, functional limitations), relationship health (relationship quality, coping with parental demands, social support), and economic health (major financial problems, financial insecurity, homelessness, employment status) were assessed at T2. Covariates, assessed at T1, included demographics, military characteristics, mental health, problem drinking, and physical health.Of the 3448 participants, 2625 (76.1%) were male, 217 (6.3%) were Hispanic, 293 (8.5%) were non-Hispanic Black, and 2690 (78.0%) were non-Hispanic White; the mean (SD) age was 40.1 (8.5) years; 826 (24.0%) met criteria for problematic anger. Prevalence of problematic anger was 15.9% (95% CI, 12.2%-19.7%) 24 months prior to military separation and 31.2% (95% CI, 26.2%-36.2%) 24 months following separation. After adjusting for covariates, problematic anger was associated with greater likelihood of behavioral and functional health outcomes (eg, posttraumatic stress disorder: adjusted odds ratio, 1.55, 95% CI, 1.23-1.96), relationship health difficulties (eg, low social support: aOR, 1.66; 95% CI, 1.23-2.24), and economic difficulties (eg, substantial financial insecurity: aOR, 1.64; 95% CI, 1.13-2.39) at T2.This cohort study found an association between prevalence of problematic anger during the military-to-civilian transition and problematic anger with subsequent adjustment difficulties among US service members. These findings suggest the need to equip service members proactively with skills to identify and manage anger as a way to support them before and during this period of transition.
Estimating Weekly National Opioid Overdose Deaths in Near Real Time Using Multiple Proxy Data Sources
Authors: Steven A. Sumner, Daniel Bowen, Kristin Holland, Marissa L. Zwald, Alana Vivolo-Kantor, Gery P. Guy, William J. Heuett, DeMia P. Pressley, Christopher M. Jones
Journal: JAMA Network Open (2022)

Opioid overdose is a leading public health problem in the United States; however, national data on overdose deaths are delayed by several months or more.To build and validate a statistical model for estimating national opioid overdose deaths in near real time.In this cross-sectional study, signals from 5 overdose-related, proxy data sources encompassing health, law enforcement, and online data from 2014 to 2019 in the US were combined using a LASSO (least absolute shrinkage and selection operator) regression model, and weekly predictions of opioid overdose deaths were made for 2018 and 2019 to validate model performance. Results were also compared with those from a baseline SARIMA (seasonal autoregressive integrated moving average) model, one of the most used approaches to forecasting injury mortality.Time series data from 2014 to 2019 on emergency department visits for opioid overdose from the National Syndromic Surveillance Program, data on the volume of heroin and synthetic opioids circulating in illicit markets via the National Forensic Laboratory Information System, data on the search volume for heroin and synthetic opioids on Google, and data on post volume on heroin and synthetic opioids on Twitter and Reddit were used to train and validate prediction models of opioid overdose deaths.Model-based predictions of weekly opioid overdose deaths in the United States were made for 2018 and 2019 and compared with actual observed opioid overdose deaths from the National Vital Statistics System.Statistical models using the 5 real-time proxy data sources estimated the national opioid overdose death rate for 2018 and 2019 with an error of 1.01% and -1.05%, respectively. When considering the accuracy of weekly predictions, the machine learning-based approach possessed a mean error in its weekly estimates (root mean squared error) of 60.3 overdose deaths for 2018 (compared with 310.2 overdose deaths for the SARIMA model) and 67.2 overdose deaths for 2019 (compared with 83.3 overdose deaths for the SARIMA model).Results of this serial cross-sectional study suggest that proxy administrative data sources can be used to estimate national opioid overdose mortality trends to provide a more timely understanding of this public health problem.
Therapy for Mild to Moderate Asthma
Authors: Sarah E. Gray, Adam S. Cifu, Valerie G. Press
Journal: JAMA (2022)

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An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial
Authors: Giuseppe Della Pepa, Valentina Brancato, Giuseppina Costabile, Dominic Salamone, Alessandra Corrado, Marilena Vitale, Carlo Cavaliere, Marcello Mancini, Marco Salvatore, Delia Luongo, Gabriele Riccardi, Angela A. Rivellese, Giovanni Annuzzi, Lutgarda Bozzetto
Journal: Diabetes Care (2022)

OBJECTIVE To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS According to a randomized controlled parallel-group design, 39 individuals with T2D, 35–75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. RESULTS After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0–120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = −0.383; P = 0.023). CONCLUSIONS In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.
Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis
Authors: Ricardo Moreno Traspas, Tze Shin Teoh, Pui-Mun Wong, Michael Maier, Crystal Y. Chia, Kenneth Lay, Nur Ain Ali, Austin Larson, Fuad Al Mutairi, Nouriya Abbas Al-Sannaa, Eissa Ali Faqeih, Majid Alfadhel, Huma Arshad Cheema, Juliette Dupont, Stéphane Bézieau, Bertrand Isidor, Dorrain Yanwen Low, Yulan Wang, Grace Tan, Poh San Lai, Hugues Piloquet, Madeleine Joubert, Hulya Kayserili, Kimberly A. Kripps, Shareef A. Nahas, Eric P. Wartchow, Mikako Warren, Gandham SriLakshmi Bhavani, Majed Dasouki, Renata Sandoval, Elisa Carvalho, Luiza Ramos, Gilda Porta, Bin Wu, Harsha Prasada Lashkari, Badr AlSaleem, Raeda M. BaAbbad, Anabela Natália Abreu Ferrão, Vasiliki Karageorgou, Natalia Ordonez-Herrera, Suliman Khan, Peter Bauer, Benjamin Cogne, Aida M. Bertoli-Avella, Marie Vincent, Katta Mohan Girisha, Bruno Reversade
Journal: Nature Genetics (2022)
TFEB induces mitochondrial itaconate synthesis to suppress bacterial growth in macrophages
Authors: Ev-Marie Schuster, Maximilian W. Epple, Katharina M. Glaser, Michael Mihlan, Kerstin Lucht, Julia A. Zimmermann, Anna Bremser, Aikaterini Polyzou, Nadine Obier, Nina Cabezas-Wallscheid, Eirini Trompouki, Andrea Ballabio, Jörg Vogel, Joerg M. Buescher, Alexander J. Westermann, Angelika S. Rambold
Journal: Nature Metabolism (2022)

Abstract Successful elimination of bacteria in phagocytes occurs in the phago-lysosomal system, but also depends on mitochondrial pathways. Yet, how these two organelle systems communicate is largely unknown. Here we identify the lysosomal biogenesis factor transcription factor EB (TFEB) as regulator for phago-lysosome-mitochondria crosstalk in macrophages. By combining cellular imaging and metabolic profiling, we find that TFEB activation, in response to bacterial stimuli, promotes the transcription of aconitate decarboxylase (Acod1, Irg1) and synthesis of its product itaconate, a mitochondrial metabolite with antimicrobial activity. Activation of the TFEB–Irg1–itaconate signalling axis reduces the survival of the intravacuolar pathogen Salmonella enterica serovar Typhimurium. TFEB-driven itaconate is subsequently transferred via the Irg1-Rab32–BLOC3 system into the Salmonella -containing vacuole, thereby exposing the pathogen to elevated itaconate levels. By activating itaconate production, TFEB selectively restricts proliferating Salmonella , a bacterial subpopulation that normally escapes macrophage control, which contrasts TFEB’s role in autophagy-mediated pathogen degradation. Together, our data define a TFEB-driven metabolic pathway between phago-lysosomes and mitochondria that restrains Salmonella Typhimurium burden in macrophages in vitro and in vivo.
Origin and function of activated fibroblast states during zebrafish heart regeneration
Authors: Bo Hu, Sara Lelek, Bastiaan Spanjaard, Hadil El-Sammak, Mariana Guedes Simões, Janita Mintcheva, Hananeh Aliee, Ronny Schäfer, Alexander M. Meyer, Fabian Theis, Didier Y. R. Stainier, Daniela Panáková, Jan Philipp Junker
Journal: Nature Genetics (2022)

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.
Reply
Authors: Kwang Yoon Kim, Kyung‐Won Hong, Bom Taeck Kim
Journal: Hepatology (2022)

We would like to thank you for your comment regarding a new perspective on the genetic bases of developing alcoholic liver disease (ALD). It is evident that people with a genetically low enzyme activity of aldehyde dehydrogenase (ALDH) have unpleasant bodily reactions such as headache, nausea, palpitations, facial flushing, and drowsiness, which are related to the blood level of acetaldehyde soaring immediately after drinking even a small amount of alcohol.[1] A polymorphism of the ALDH2 gene common in East Asians may be associated with the high incidence of ALD in East Asians, for they share a geographic distribution.[2] A polymorphism of ALDH2 that attenuates acetaldehyde metabolism can lead to acetaldehyde accumulation. For its electrophilic property, accumulated acetaldehyde binds to biomolecules like proteins or DNA to cause cellular damage and may result in ALD.[3] However, genetic studies have demonstrated contradictory results to the proposed hypothesis. In a meta‐analysis of 12 studies investigating East Asian populations regarding ALDH2 polymorphisms, the risk of alcoholic liver cirrhosis was higher in those with the ALDH2*1 allele than in those with the ALDH2*2/*2 allele, which is a mutant with a low protective effect against ethanol.[4] These findings were also found in a study conducted in a Korean population. In addition, the ALDH2 gene did not show any statistically significant relationship with the occurrence of ALD in any drinking group in our study.[5] These series of studies suggest that key mechanisms related to ALD development are uncontrolled inflammation, reduced antioxidant defense, and entangled telomere recombination, which are also identified in our study rather than the metabolic ability of acetaldehyde. CONFLICT OF INTEREST Nothing to report.
Lifetime risk of developing diabetes in Chinese people with normoglycemia or prediabetes: A modeling study
Authors: Xinge Zhang, Hongjiang Wu, Baoqi Fan, Mai Shi, Eric S. H. Lau, Aimin Yang, Elaine Chow, Alice P. S. Kong, Juliana C. N. Chan, Ronald C. W. Ma, Andrea O. Y. Luk
Journal: PLoS Medicine (2022)

Little is known about the lifetime risk of progression to diabetes in the Asian population. We determined remaining lifetime risk of diabetes and life years spent with diabetes in Chinese people with normoglycemia and prediabetes.Using territory-wide diabetes surveillance data curated from electronic medical records of Hong Kong Hospital Authority (HA), we conducted a population-based cohort study in 2,608,973 individuals followed from 2001 to 2019. Prediabetes and diabetes were identified based on laboratory measurements, diagnostic codes, and medication records. Remaining lifetime risk and life years spent with diabetes were estimated using Monte Carlo simulations with state transition probabilities based on a Markov chain model. Validations were performed using several sensitivity analyses and modified survival analysis. External replication was performed using the China Health and Retirement Longitudinal Survey (CHARLS) cohort (2010 to 2015). The expected remaining lifetime risk of developing diabetes was 88.0 (95% confidence intervals: 87.2, 88.7)% for people with prediabetes and 65.9 (65.8, 65.9)% for people with normoglycemia at age 20 years. A 20-year-old person with prediabetes would live with diabetes for 32.5 (32.0, 33.1) years or 51.6 (50.8, 52.3)% of remaining life years, whereas a person with normoglycemia at 20 years would live 12.7 (12.7, 12.7) years with diabetes or 18.4 (18.4, 18.5)% of remaining life years. Women had a higher expected remaining lifetime risk and longer life years with diabetes compared to men. Results are subjected to possible selection bias as only people who undertook routine or opportunistic screening were included.These findings suggest that Hong Kong, an economically developed city in Asia, is confronted with huge challenge of high lifetime risk of diabetes and long life years spent with diabetes, especially in people with prediabetes. Effective public health policies and targeted interventions for preventing progression to diabetes are urgently needed.
The MI-PICC Score: A Risk-Prediction Model for PICC-associated Complications in the ICU
Authors: Sushant Govindan, Megan E. O’Malley, Scott A. Flanders, Vineet Chopra
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"The MI-PICC Score: A Risk-Prediction Model for PICC-associated Complications in the ICU." American Journal of Respiratory and Critical Care Medicine, 206(10), pp. 1286–1289
Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial
Authors: Annelie Johansson, Huma Dar, Laura J. van ’t Veer, Nicholas P. Tobin, Gizeh Perez-Tenorio, Anna Nordenskjöld, Ulla Johansson, Johan Hartman, Lambert Skoog, Christina Yau, Christopher C. Benz, Laura J. Esserman, Olle Stål, Bo Nordenskjöld, Tommy Fornander, Linda S. Lindström
Journal: Journal of Clinical Oncology (2022)

PURPOSE To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. METHODS Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node–positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years. RESULTS In estrogen receptor–positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed ( P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit. CONCLUSION This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor–positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
The interplay of gut microbiota between donors and recipients determines the efficacy of fecal microbiota transplantation
Authors: Ruiqiao He, Pan Li, Jinfeng Wang, Bota Cui, Faming Zhang, Fangqing Zhao
Journal: Gut Microbes (2022)

Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis associated diseases, such as
Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals
Authors: Stijn P. Andeweg, Harry Vennema, Irene Veldhuijzen, Naomi Smorenburg, Dennis Schmitz, Florian Zwagemaker, Arianne B. van Gageldonk-Lafeber, Susan J. M. Hahné, Chantal Reusken, Mirjam J. Knol, Dirk Eggink
Journal: Science Translational Medicine (2022)

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.